The aims of the program are: to identify mechanisms underlying normal mammalian differentiation, especially in relation to gene control; to understand the developmental basis for genetic defects or diseases, and malignancy; and to learn what maternal factors are critical for embryo development. These goals are being pursued in four experimental systems: I. Allophenic mice. In these animals, cells of different genotypes are experimentally associated in early cleavage and coexist throughout development. With appropriate genetic markers, gene control of normal development is being analyzed in the intact organism. The developmental basis for a number of genetically caused disorders will be investigated in allophenic animals comprising normal and genetically defective cells, or tumor-susceptible and non-susceptible cell strains. II. Teratocarcinomas. Transplantable mouse teratocarcinomas afford a large supply of undifferentiated multipotential cells for experimental purposes. They will be used to analyze the characteristics of the multipotential state, the earliest events in cell diversification, and the developmental and genetic aberrations in carcinogenesis. III. Haploid mammalian cells. A teratocarcinoma haploid cell line would be especially valuable for mutagenesis experiments and genetic analyses of regulatory systems and differentiation. Efforts to derive such a line will be made with ovarian teratomas of parthenogenetic origin in the LT mouse strain. IV. Implantation is essential for ongoing development of the embryo and may offer avenues of experimental fertility control. Uterine-embryo interrelationships are under study in the mouse, where an estrogen-controlled uterine proteinase is a critical factor for initiation of implantation.